CA2730710A1 - Utilisation therapeutique d'un facteur de croissance, metrnl - Google Patents
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
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- Neurosurgery (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
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- Biochemistry (AREA)
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- Psychology (AREA)
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- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
La présente invention concerne le domaine de l'utilisation thérapeutique de protéines, de gènes et de cellules. L'invention porte plus particulièrement sur la thérapie basée sur la fonction biologique d'une protéine thérapeutique secrétée, METRNL, notamment dans le traitement de troubles du système nerveux. METRNL est un facteur de croissance et de survie des cellules nerveuses qui présente des effets neuroprotecteurs et/ou de neurogenèse.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8331608P | 2008-07-24 | 2008-07-24 | |
| US61/083,316 | 2008-07-24 | ||
| DKPA200801036 | 2008-07-24 | ||
| DKPA200801036 | 2008-07-24 | ||
| PCT/DK2009/050165 WO2010009732A1 (fr) | 2008-07-24 | 2009-07-07 | Utilisation thérapeutique d'un facteur de croissance, metrnl |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2730710A1 true CA2730710A1 (fr) | 2010-01-28 |
| CA2730710C CA2730710C (fr) | 2021-06-08 |
Family
ID=41314584
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2730710A Active CA2730710C (fr) | 2008-07-24 | 2009-07-07 | Utilisation therapeutique d'un facteur de croissance, metrnl |
Country Status (10)
| Country | Link |
|---|---|
| US (4) | US8334264B2 (fr) |
| EP (1) | EP2195013B1 (fr) |
| JP (1) | JP5616888B2 (fr) |
| CN (1) | CN102164611B (fr) |
| AT (1) | ATE531383T1 (fr) |
| AU (1) | AU2009273600B2 (fr) |
| CA (1) | CA2730710C (fr) |
| DK (1) | DK2195013T3 (fr) |
| HK (1) | HK1145070A1 (fr) |
| WO (1) | WO2010009732A1 (fr) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8334264B2 (en) * | 2008-07-24 | 2012-12-18 | NsGenee A/S | Therapeutic use of a growth factor, METRNL |
| WO2012041328A1 (fr) * | 2010-10-01 | 2012-04-05 | Nsgene A/S | Traitement de l'allodynie, de l'hyperalgésie, de la douleur spontanée et de la douleur illusionnelle |
| CN107596346A (zh) * | 2011-09-05 | 2018-01-19 | 霍巴治疗公司 | 异常性疼痛、痛觉过敏、自发性疼痛、和幻痛的治疗 |
| US10717992B2 (en) * | 2013-01-25 | 2020-07-21 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for regulating thermogenesis and muscle inflammation using metrnl and metrn |
| WO2014183207A1 (fr) * | 2013-05-17 | 2014-11-20 | Exerkine Corporation | Méthode thérapeutique de traitement du syndrome métabolique |
| CN103536904B (zh) * | 2013-10-29 | 2015-02-18 | 中国人民解放军第二军医大学 | Metrnl蛋白在制备降血糖药物方面的应用 |
| WO2015062167A1 (fr) * | 2013-10-29 | 2015-05-07 | 中国人民解放军第二军医大学 | Application d'une protéine metrnl dans la préparation d'un médicament hypolipidémique, anti-hypertenseur |
| CN103536903B (zh) * | 2013-10-29 | 2015-04-15 | 中国人民解放军第二军医大学 | Metrnl蛋白在制备降血脂药物方面的应用 |
| US11434501B2 (en) | 2014-08-28 | 2022-09-06 | Board Of Trustees Of Michigan State University | Sprr1A as a genetic target for treating neurodegenerative diseases |
| US9687483B2 (en) * | 2015-01-26 | 2017-06-27 | BioAxone BioSciences, Inc. | Treatment of cerebral cavernous malformations and cerebral aneurysms with Rho kinase inhibitors |
| US10857157B2 (en) | 2015-01-26 | 2020-12-08 | BioAxone BioSciences, Inc. | Treatment of cerebral cavernous malformations and cerebral aneurysms with rho kinase inhibitors |
| US10149856B2 (en) | 2015-01-26 | 2018-12-11 | BioAxone BioSciences, Inc. | Treatment of cerebral cavernous malformations and cerebral aneurysms with rho kinase inhibitors |
| US10106525B2 (en) | 2015-01-26 | 2018-10-23 | BioAxone BioSciences, Inc. | Rho kinase inhibitor BA-1049 (R) and active metabolites thereof |
| CN104977415A (zh) * | 2015-03-09 | 2015-10-14 | 中国人民解放军第二军医大学 | Metrnl蛋白作为炎症性肠病诊断血清标志物的应用及其试剂盒 |
| CN104808004B (zh) * | 2015-05-06 | 2017-03-01 | 中国人民解放军第二军医大学 | Metrnl蛋白作为结肠癌诊断标志物的应用及试剂盒 |
| KR101586054B1 (ko) * | 2015-11-20 | 2016-01-21 | 고려대학교 산학협력단 | 메테오린-유사체 (meteorin-like)를 포함하는 유방암의 예방 또는 치료용 조성물 |
| CN107088223B (zh) * | 2016-02-17 | 2020-07-07 | 中国人民解放军第二军医大学 | Metrnl蛋白或基因在治疗内皮功能受损中的应用 |
| DE102016204700A1 (de) | 2016-03-22 | 2017-09-28 | Universität Rostock | Rekombinante Herstellung von Subfatin |
| CN107537025B (zh) * | 2016-06-23 | 2020-01-10 | 上海风劲生物医药科技有限公司 | Metrnl蛋白或基因在调节抗菌肽表达中的应用 |
| US11198680B2 (en) | 2016-12-21 | 2021-12-14 | BioAxone BioSciences, Inc. | Rho kinase inhibitor BA-1049 (R) and active metabolites thereof |
| WO2018165183A1 (fr) * | 2017-03-06 | 2018-09-13 | Tactus Therapeutics, Inc. | Formulations d'opioïdes de dissuasion à l'abus |
| US10537567B2 (en) | 2017-07-11 | 2020-01-21 | BioAxone BioSciences, Inc. | Kinase inhibitors for treatment of disease |
| AU2018356538B2 (en) * | 2017-10-25 | 2023-09-28 | Nouscom Ag | Eukaryotic cell line |
| CN110227146A (zh) * | 2018-03-06 | 2019-09-13 | 上海风劲生物医药科技有限公司 | Metrnl蛋白或基因在防治认知障碍方面的应用 |
| WO2020056056A1 (fr) * | 2018-09-12 | 2020-03-19 | Hough Ear Institute | Procédés de traitement d'une perte d'audition consécutive à une chirurgie d'implant cochléaire |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69221484T2 (de) | 1991-04-25 | 1998-02-19 | Univ Brown Res Found | Implantierbare, biokompatible immunisolator-trägersubstanz zum abgeben ausgesuchter, therapeutischer produkte |
| PT639225E (pt) * | 1992-04-30 | 2003-03-31 | Innogenetics Nv | Polipeptidos e peptidos novos acidos nucleicos que codificam para aqueles e sua utilizacao na area da terapia tumoral inflamacao ou imunologia |
| ATE218893T1 (de) | 1993-08-12 | 2002-06-15 | Neurotech Sa | Biokompatible immunoisolatorische kapseln, die genetisch veränderte zellen enthalten |
| US6027721A (en) | 1996-05-20 | 2000-02-22 | Cytotherapeutics, Inc. | Device and method for encapsulated gene therapy |
| WO2001025427A1 (fr) | 1999-10-01 | 2001-04-12 | Kyowa Hakko Kogyo Co., Ltd. | Adn reagissant a la contrainte de cisaillement |
| CA2390415A1 (fr) | 1999-11-30 | 2001-06-07 | Innogenetics N.V. | Nouvelles utilisations des facteurs d'activation des macrophages suppresseurs |
| WO2001055320A2 (fr) | 2000-01-31 | 2001-08-02 | Human Genome Sciences, Inc. | Acides nucleiques, proteines et anticorps |
| WO2001055440A1 (fr) | 2000-01-31 | 2001-08-02 | Human Genome Sciences, Inc. | Acides nucleiques, proteines et anticorps |
| EP1572987A4 (fr) | 2000-02-03 | 2005-11-30 | Nuvelo Inc | Acides nucleiques et polypeptides |
| EP1280815A1 (fr) | 2000-05-02 | 2003-02-05 | Human Genome Sciences, Inc. | 29 proteines humaines secretees |
| US20050208062A1 (en) | 2001-12-21 | 2005-09-22 | Yongming Sun | Compositions and methods relating to hepatic specific genes and proteins |
| WO2004035732A2 (fr) | 2002-08-29 | 2004-04-29 | Five Prime Therapeutics, Inc. | Polypeptides humains codes par des polynucleotides et procedes d'utilisation de ces polypeptides |
| WO2004079014A2 (fr) | 2003-03-04 | 2004-09-16 | Arcturus Bioscience, Inc. | Signatures de statut er d'un cancer du sein |
| NZ550542A (en) | 2004-03-30 | 2009-03-31 | Nsgene As | Therapeutic use of a growth factor, NsG33 |
| WO2006110593A2 (fr) * | 2005-04-07 | 2006-10-19 | Macrogenics, Inc. | Cibles biologiques pour le diagnostic, le traitement et la prevention du cancer |
| US8334264B2 (en) | 2008-07-24 | 2012-12-18 | NsGenee A/S | Therapeutic use of a growth factor, METRNL |
| WO2012041328A1 (fr) | 2010-10-01 | 2012-04-05 | Nsgene A/S | Traitement de l'allodynie, de l'hyperalgésie, de la douleur spontanée et de la douleur illusionnelle |
| CN107596346A (zh) | 2011-09-05 | 2018-01-19 | 霍巴治疗公司 | 异常性疼痛、痛觉过敏、自发性疼痛、和幻痛的治疗 |
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| CN102164611A (zh) | 2011-08-24 |
| US20110112035A1 (en) | 2011-05-12 |
| AU2009273600B2 (en) | 2013-04-18 |
| EP2195013B1 (fr) | 2011-11-02 |
| HK1145070A1 (en) | 2011-04-01 |
| WO2010009732A1 (fr) | 2010-01-28 |
| ATE531383T1 (de) | 2011-11-15 |
| EP2195013A1 (fr) | 2010-06-16 |
| US20170333526A1 (en) | 2017-11-23 |
| US9675669B2 (en) | 2017-06-13 |
| DK2195013T3 (da) | 2012-02-06 |
| US20130267464A1 (en) | 2013-10-10 |
| US8334264B2 (en) | 2012-12-18 |
| CA2730710C (fr) | 2021-06-08 |
| JP2011528558A (ja) | 2011-11-24 |
| US9068015B2 (en) | 2015-06-30 |
| CN102164611B (zh) | 2015-01-07 |
| JP5616888B2 (ja) | 2014-10-29 |
| US20160045564A1 (en) | 2016-02-18 |
| AU2009273600A1 (en) | 2010-01-28 |
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